Human arylamine N-acetyltransferase 1 (NAT1) as a target of chemotherapeutic drugs in breast cancer: cisplatin as a model

Abstract

Human arylamine N -acetyltransferase 1 (NAT1) is a phase II xenobiotic-metabolizing enzyme (XME) involved in the biotransformation of many aromatic amines and heterocyclic amines. This XME is known to play important roles in both the detoxication and/or bioactivation of numerous drugs and carcinogens. NAT1 is a polymorphic enzyme with a large tissue distribution. NAT1 polymorphisms and activity have been extensively studied because of its potential role in the biotransformation of important carcinogens. Several recent studies suggest that NAT1 may have a role in breast cancer progression. Indeed, this XME has been shown to affect the growth and drug resistance of breast cancer cells and appears to be a marker in human estrogen receptor positive breast cancer. Here we provide an overview of our recently published results indicating that NAT1 is a new target of the anticancer drug cisplatin in breast cancer cells. Moreover, these results are discussed in light of the data showing inhibition of human NAT1 and its mouse orthologue by natural and synthetic estrogens.